CN1573332A - Blood sugar level measuring apparatus - Google Patents

Abstract

Blood sugar levels are measured non-invasively based on temperature measurement. Measured blood sugar levels are corrected using blood oxygen saturation and blood flow volume. The measurement data is further stabilized by taking into consideration the influences of interfering substances on blood oxygen saturation.

Description

Determination of blood glucose level equipment

Technical field

The present invention relates under the condition of not carrying out blood sampling, the concentration of glucose in the biological living be carried out method for measuring of non-invasion formula and equipment.

Background technology

People such as Hilson once were reported in the diabetic were carried out can causing behind the vein glucose injection its face and sublingual temperature change (non-patent literature 1).People such as Scott also discussed diabetes and the such problem (non-patent literature 2) of body heat regulation.According to these research, people such as Cho have advised corresponding method and apparatus, only are used for by to the measurement of temperature and do not need to collect blood sample and just can determine blood concentration of glucose (patent documentation 1 and 2).

In addition, carried out various trials under the condition of not carrying out blood sampling, measuring concentration of glucose.For example, there is a kind of method (patent documentation 3) to advise the measuring point being shone, and surveys the temperature that sees through light intensity and biological living with the near infrared light of three wavelength.Then, calculate the typical value of the second differential value of absorptance, and according to the temperature of the biosome that records and the difference between the reference temperature of formerly determining above-mentioned typical value is proofreaied and correct.Thereby can determine with proofread and correct after the corresponding blood sugar concentration of typical value.Corresponding apparatus (patent documentation 4) also is provided simultaneously, has utilized this equipment when monitoring the temperature of biosome, to raise or reduce the temperature of measuring point.When temperature changes, measure obtain based on light-struck optical attenuation degree, thereby just can record the concentration of glucose, wherein the concentration of glucose causes temperature to depend on the degree of optical attenuation.In addition, also report has a kind of like this equipment (patent documentation 5), can obtain the output ratio between the light of seeing through by this equipment with reference to light and illuminated sample, then can be by the logarithm of output ratio and the concentration that the linear relationship between the biosome temperature calculates glucose.

The suggestion of another kind method is accurately determined concentration of glucose (patent documentation 6) by merging to proofread and correct.In the method, measurement result mainly is as these several phenomenons of infrared absorption, scattering and polariscopy, and they are used for determining concentration of glucose together.In another approach, be in optical measuring system by after the influence of eliminating other component materials beyond the glucose, measure and the result proofreaied and correct (patent documentation 7).The influence of removing uncorrelated component not only is used in the determination of glucose, and can be used in the measurement to other material.For example, the influence (patent documentation 8) that uncorrelated component is removed in suggestion when oxygen expenditure amount in the measurement human body or oxygen content.

(non-patent literature 1)

R.M Hilson and T.D.R Hockaday, " Facial and sublingual temperaturechanges following intravenous glucose injection in diabetics, " Diabete ﹠amp; Metabolisme, 8, pp.15-19:1982

(non-patent literature 2)

A.R?Scott，T.Bennett，I.A?MacDonald，“Diabetes?mellitus?andthermoregulation，”Can.J.Physiol.Pharmacol.，65，pp.1365-1376：1787

(patent documentation 1)

U.S. Patent number: 5,924,996

(patent documentation 2)

U.S. Patent number: 5,795,305

(patent documentation 3)

Japanese patent application publication No.: 2000-258343 A

(patent documentation 4)

Japanese patent application publication No.: 10-33512A (1998)

(patent documentation 5)

Japanese patent application publication No.: 10-108857A (1998)

(patent documentation 6)

Japanese patent application publication No.: 2001-524342A

(patent documentation 7)

Japanese patent application publication No.: 10-325794A (1998)

(patent documentation 8)

Japanese patent application publication No.: 2003-517342As

The glucose oxidase that glucose in the blood (blood sugar) is used for carrying out in the cell reacts to produce keeps the necessary energy of biosome.Especially under basal metabolic state, the most of energy that is produced is changed into the temperature that heat energy is used to keep biosome.Therefore, there is certain contact in deducibility between blood glucose concentration and body temperature.Yet when the sick adstante febre that causes, clearly body temperature also can change because of the influence of the other factors except that the blood concentration of glucose.Although have the method for determining blood sugar concentration when not carrying out blood sampling by temperature measuring, they still lack enough accuracies.

Invent out according to emission light, determine the method for concentration of glucose as the near infrared light intensity.Yet, because the feature of the absorption peak of near infrared light is not clearly, so be difficult to use these methods to analyze accurately.In order to address this problem, to have proposed to use alignment technique to eliminate interfering material in the light measurement system, but do not had a kind of can enough be accurate to be used for actual use in them.

Summary of the invention

Purpose of the present invention just provides a kind of method and apparatus, makes that the temperature data according to the person under inspection is very accurately determined its blood sugar concentration under the condition of not carrying out blood sampling.

Blood sugar is transported in the cell in the whole human body by vascular system, especially capillary.In human body, there is complicated metabolic pathway.Glucose oxidase is a kind of reaction, in this reaction, at first is that the reaction of blood sugar and oxygen produces water, carbon dioxide and energy.The oxygen here is meant by the oxygen of blood transport in the cell.The volume of oxygen supply is determined by the volume of hemoglobin concentration, hemoglobin saturation with oxygen and blood flow.On the other hand, producing heat by glucose oxidase in the body dissipates in body by modes such as convection current, heat radiation, conduction.Suppose the energy that body temperature is produced by glucose burning in the body, the balance between instant heating output and the heat dissipation recited above is determined, the model below inventors have set up:

(1) amount of the amount of hot output and heat dissipation is considered to equate.

(2) amount of hot output is the function of blood sugar concentration and oxygen supply volume.

(3) the oxygen supply volume is to be determined by the blood volume that flows in hemoglobin concentration, hemoglobin saturation with oxygen and the capillary.

(4) amount of heat dissipation is mainly determined by thermal convection and heat radiation.

According to this model, on the basis of the result by measuring the parameter that shell temperature, mensuration parameter relevant with blood oxygen concentration and mensuration is correlated with the blood flow volume, can realize accurately definite blood sugar concentration after, we have finished the present invention.These parameters can record from a certain position of human body, for example finger tip.The parameter relevant with convection current and radiation can be determined by the thermal measurement to finger tip.The parameter relevant with hemoglobin concentration and hemoglobin saturation with oxygen can by spectroscopic methodology record haemoglobin and find out the haemoglobin of taking oxygen and the haemoglobin of not taking oxygen between ratio after determine.Yet therefore the be interfered influence of material of spectral measurement is necessary these interfering materials are proofreaied and correct.Can reach this purpose by measuring the melanin in cholerythrin in the blood and absurd creature, the epidermis and the thickness and the roughness of skin, because these materials are by the main interfering material in a part of process of spectroscopy measurements human body.The parameter relevant with the blood flow volume can be determined from the heat of skin transmission by measuring.

On the one hand, a kind of blood sugar level measuring equipment provided by the invention comprises: (1) one apparatus for measuring amount of heat is used to measure a plurality of shell temperatures.The information that obtains is used to calculate the heat of the convective heat transfer that constitutes the body surface heat dissipation and the heat of radiation heat transfer.This equipment also comprises (2) one blood flow volume measurement devices, is used to obtain the information of blood flow volume.Also comprise (3) one optical measuring devices, be used for obtaining the hemoglobin concentration and the hemoglobin saturation with oxygen of blood.The light that this device comprises the light source that can generate at least three kinds of different wavelengths of light, send by light source shines an optical system and at least three kinds of different photo-detectors of body surface, is used to survey the light that is radiated on the body surface.This equipment also further comprises (4) one memory storages, be used to store blood sugar concentration and and a plurality of temperature, blood flow volume, blood hemoglobin concentration and hemoglobin saturation with oxygen and the corresponding individual parameter of blood sugar level between concern.Also comprise (5) one calculation elements, be used for the measured value that apparatus for measuring amount of heat, blood flow volume measurement device and optical measuring device provide is converted to parameter.This calculation element is also used these parameters in the relation that memory storage stores and is calculated blood sugar concentration.This equipment also further comprises (6) one display device, is used to show the blood sugar concentration that is calculated by computing equipment.Preferably, photo-detector comprises and is used to survey catoptrical first photo-detector of body surface; Survey second photo-detector of body surface scattered light; And survey by body surface and enter skin and the 3rd photo-detector of the light that from body surface, passes.Preferably, the photo measure unit uses three kinds or more kinds of, thickness and the influence of roughness hemoglobin concentration and the hemoglobin saturation with oxygen of measuring blood of the light that is preferably five kinds of wavelength by eliminating melanin in cholerythrin in the blood and absurd creature, the epidermis and skin.

On the other hand, the invention provides a kind of blood sugar level measuring equipment, comprise an ambient temperature measurement mechanism, be used to measure the temperature of surrounding environment; One body surface contact device is used for contacting with body surface; One thermal radiation temperature detector is used to measure the radiation heat that comes from body surface; And a contiguous hygrosensor, be placed on and the adjoining position of body surface contact device.This equipment also comprises an indirect temperature detector, is used to measure the temperature that has a distance with the body surface contact device, and it is set up adjoining and have the position of certain distance with the body surface contact device with heat conducting element; One heat conducting element, it connects body surface contact device and indirect temperature detector; And the light source that can produce the light of at least three kinds of different wave lengths, wherein the light of three kinds of different wave lengths is 810nm, 950nm and the third wavelength.It also comprises an optical system, the rayed body surface that it uses light source to send; And at least three kinds of different photo-detectors, it is used to survey the light of irradiation body surface.This equipment also further comprises a storage unit, be used to store ambient temperature detector, radiation temperature detector, contiguous hygrosensor, indirect temperature detector and at least three kinds of different photo-detectors separately output and the relation between the blood sugar concentration.This equipment also further comprises a calculation element, and it uses various outputs and calculates blood sugar concentration with reference to the relation that is stored in the storage unit.This equipment also comprises a display device, is used to show the blood sugar concentration that is calculated by computing equipment.

Description of drawings

Fig. 1 has shown the Launching Model of light under the situation of using continuous light source irradiation skin surface.

Fig. 2 has shown that heat is delivered to the model of certain block from body surface.

Fig. 3 has marked and drawed temperature T ₁And T ₂Measured value variation relation in time.

Fig. 4 has shown the measurement temperature T ₃An example over time.

Relation between measured value that is provided by various sensors and the parameter that therefrom obtains has been provided Fig. 5.

Fig. 6 has shown the vertical view according to non-intrusion type measurement of blood sugar concentration device of the present invention.

Fig. 7 has shown the operating process of equipment.

Fig. 8 has shown measuring equipment in detail.

Fig. 9 has shown the concept map of the flow chart of data processing in the description equipment.

Figure 10 has marked and drawed glucose concentration value that calculates by the present invention and the glucose concentration value that records by the enzyme electrode method.

Embodiment

With reference now to accompanying drawing, the preferred embodiments of the present invention is described.

At first, will above-mentioned model be described in more detail.For the heat dissipation amount, one of its most important reason is a convective heat transfer, and it is relevant with temperature difference between surrounding environment (indoor) temperature and the shell temperature.According to the Stefan-Boltzmann rule, cause the heat radiation of main cause of heat rejection by another kind and the heat of the consumption that causes is directly proportional with the biquadratic of shell temperature.Hence one can see that, and the amount of human body heat dissipation is relevant with room temperature and shell temperature.On the other hand, the oxygen-supplying amount of another principal element relevant with thermal yield can be expressed as the product of hemoglobin concentration, hemoglobin saturation with oxygen and blood flow volume.

Hemoglobin concentration can wherein at this wavelength place, be taken the oxygen haemoglobin and equate (absorbing wavelength that equates) with the molar absorption coefficient of not taking the oxygen haemoglobin by measuring in the absorptance at a certain wavelength place.Hemoglobin saturation with oxygen can be by measuring the absorptance at same absorbent wavelength place, and measure in the absorptance at least a different wave length place, wherein at least a different wavelength place, taking the oxygen haemoglobin is known with the ratio of not taking the molar absorption coefficient of oxygen haemoglobin, finds the solution simultaneous equations then.Yet,, just must proofread and correct the influence of interference component in order to come to determine exactly hemoglobin concentration and hemoglobin saturation with oxygen by absorptivity.The interference component that influences absorptivity comprises in the color of thickness, skin of the roughness of skin surface, skin (epidermis) and the blood other interference component.These interference components can be measured by the whole bag of tricks, and the embodiment of measurement will be described below.

The roughness of skin surface can compare with scattered light by the reflected light (direct reflection) with skin surface and record.When skin surface when minute surface is smooth, can be observed the very strong and scattered light of reflected light a little less than.On the contrary, when pachylosis, the difference between reflected light and scattered light will diminish.Therefore, by determining the ratio between reflected light and the scattered light, just can estimate the roughness of skin.

The thickness of skin can be measured by measurement light intensity of travel distance d in skin.Fig. 1 has shown the behavior of the light when skin surface is subjected to the irradiation of continuous light.When the light that uses certain wavelength and intensity shone, light was subjected to the reflection and the scattering of skin surface.Part light transdermal and repeat scattering and diffusion.The degree of depth that the light of this behavior is penetrated when stroke is d is a constant that depends on wavelength substantially.Skin does not contain blood, therefore has low flowability, thereby causes the low absorptivity to light.On the other hand, contain blood in the corium, therefore have high flowability, thereby cause high-absorbility light.Therefore, when skin was thin, light can deeper penetrate corium, thereby causes bigger absorptivity.When skin was thick, it is shorter that the distance that light is advanced just becomes, thereby absorptivity diminishes.By obtain light intensity that stroke is d and light in an identical manner in standard substance stroke be the ratio of the light intensity of known thickness, thereby can estimate the thickness of skin.

The color of skin can be determined by melanic absorption spectrum.

In blood, there are two kinds of main interference compositions.A kind of is cholerythrin, and it is one of origin cause of formation of jaundice symptom.Another kind is an absurd creature, and it is one of origin cause of formation of high fat of blood symptom.The concentration of these compositions also can be determined by absorption spectrum.

Therefore, hemoglobin concentration and hemoglobin saturation with oxygen can be determined in the absorptance of the light at two kinds of wavelength places by measurement at least, at this moment, take that the oxygen haemoglobin equates with the ratio of not taking the molar absorption coefficient between the oxygen haemoglobin or known, and in the light time of using three kinds of wavelength, the molar absorption coefficient of melanin, cholerythrin and absurd creature is known.To use three kinds of detectors at least in the measurement, the promptly main mobile photon detector of surveying catoptrical reflection light detector, mainly surveying the detector for scattered light of scattered light and mainly survey mobile photon.

Reflection light detector be except can surveying from most of reflected light of body surface reflection, can also the probe portion scattered light, and this scattered light is the light that leaves from body surface then by body interior.Therefore, the reflected light that detected and the ratio between the scattered light can be obtained, thereby the degree of roughness of skin can be estimated.Detector for scattered light except can survey most of by body interior then from the scattered light that body surface leaves, can also probe portion from the reflected light of body surface reflection.Therefore, can carry out the measurement of suitable absorptance, it relates to hemoglobin concentration, hemoglobin saturation with oxygen, melanin, cholerythrin and/or absurd creature.Mobile photon is blocked on the optics to the path of mobile photon detector, thereby mobile photon detector can not detect the light that those come from reflected light and scattered light.Therefore, mobile photon detector only can be surveyed mobile photon, thereby can estimate the thickness of skin.In the process of surveying, need to use at least three kinds of detectors altogether, i.e. reflection light detector, detector for scattered light and mobile photon detector.Preferably, that also can use other has identity function and a more highly sensitive detector, and its sensitivity depends on the light wavelength kind.In addition, can also use the emission photo-detector to survey those light as needs by search coverage.In this case, by catching blood pulses, can also improve the accuracy of measurement.

The value of wavelength described herein is best suited for being used for the absorptance that obtains to expect, as obtaining absorptance or obtain absorption peak under the condition of identical molar absorption coefficient.Therefore, the light of the wavelength of approaching description value here can be used to similar measurement.

Remaining is the blood flow volume, and it can be measured by the whole bag of tricks.To be described an embodiment below.

Fig. 2 has shown that heat is delivered to the model of certain solid block with certain thermal capacitance from body surface, and this block separates after the contact regular hour with body surface earlier.This block is formed from a resin, as plastics or vinyl chloride.In the example of describing, mainly concentrate on the temperature T of that part of block that contacts with body surface ₁Over time, the temperature T on the point that contacts with body surface not and on the block ₂Over time.The blood flow volume can be mainly by monitoring (point of the block of isolating in the space) temperature T ₂Estimate over time.Concrete will be explained hereinafter.

At block with before body surface contacts, the temperature T on 2 of block ₁And T ₂With room temperature T _rEquate.As shell temperature T _sBe higher than room temperature T _rThe time, because contacting with body surface, block cause heat to pass to block from body surface, thus temperature T ₁Fast rise and near shell temperature T _sOn the other hand, thus since the heat that in block, conducts from the block surface temperature T of scattering and disappearing ₂Be lower than temperature T ₁, and compare temperature T ₁Rising more relax.Temperature T ₁And temperature T ₂Depend on the heat that transmits to block from body surface over time, it depends on the blood flow volume of the capillary under the skin conversely again.If capillary is considered to heat exchanger, the coefficient of heat conductivity from the peripherad cell tissue of capillary is exactly the function of blood flow volume so.Therefore, by monitoring temperature T ₁And temperature T ₂Record over time from the heat of body surface, just can estimate the heat that transmits to cell tissue from capillary to the block transmission.According to this estimated value, thereby just can estimate the blood flow volume.Therefore, by monitoring temperature T ₁And T ₂Change in time, thus record from the heat of body surface to the block transmission, just can estimate the heat that transmits to cell tissue from capillary.According to this estimated value, the blood flow volume also can obtain estimation.

Fig. 3 has shown and that part of temperature T that contacts with body surface on block ₁Over time, leave temperature T with the body surface contact position and on block ₂Over time.When block contacts with body surface, T ₁Measured value increase sharply, and block with descend gradually after body surface separates.

Fig. 4 has shown the temperature T that records by the radiation temperature detector ₃Over time.Because this detector is surveyed the temperature of being brought because of the body surface radiation, so more responsive more than other the variation of sensor for temperature.Because radiation heat is to propagate as electromagnetic wave, thereby can immediately conduct the change of temperature.Therefore, come measuring radiation heat by the radiation temperature detector being placed near block and body surface position contacting, shown in Figure 8 as will be described, the contact start time t between block and body surface _StartWith contact concluding time t _EndCan pass through temperature T ₃Change and record.For example, as shown in Figure 4, a temperature threshold is set.Contact start time t _StartBe T ₃Time when surpassing temperature threshold.Contact concluding time t _EndBe T ₃Time when being lower than temperature threshold.For example temperature threshold is arranged on 32 ℃.

Then, at t _StartAnd t _EndBetween T ₁Measured value S type curve, for example logarithmic curve approaches.Logarithmic curve can be expressed by following equation:

$T=\frac{b}{1+c\×\exp (-a\×t)}+d$

Wherein, T is a temperature, and t is the time.

Measured value can determine that factor a, b, c and d approach by nonlinear least square method.For the resulting expression formula of approaching, with T at t _StartAnd t _EndBetween carry out the integration value of obtaining S ₁

Similarly, from T ₂Measured value calculate integrated value S ₂(S ₁-S ₂) more little, from the finger surface to T ₂The heat that transmit the position is big more.(S ₁-S ₂) along with the finger t duration of contact _Cont(=t _End-t _Start) increase and increase.Therefore, with a ₅/ (t _Cont* (S ₁-S ₂)) as parameter X ₅Be used to indicate the blood flow volume, here a ₅Be scale-up factor.

Therefore, as can be seen by above-mentioned model being used for of recording determine the necessary data of blood glucose concentration be the temperature variation of room temperature (ambient temperature), the shell temperature block that changes, contact with body surface, by the temperature of body surface radiation generation and reflected light and the extinction of scattered light and the intensity of mobile photon of employed at least three wavelength.

Relation between measured value that is provided by various sensors and the parameter that therefrom obtains has been provided Fig. 5.Block is contacted with body surface, and two positions on block record two types temperature T by two temperature sensors ₁And T ₂Record body surface radiation temperature T separately ₃With room temperature T ₄The absorptance A of scattered light ₁And A ₂Record at least two wavelength places relevant with haemoglobin.Catoptrical absorptance A ₃, A ₄And A ₅Record at least three wavelength places relevant with absurd creature, cholerythrin and melanin.Catoptrical absorptance A ₆Record at an independent at least wavelength place.Alternatively, catoptrical absorptance can record by five kinds of above-mentioned wavelength, thereby can use the average or the intermediate value of these values.The intensity I of mobile photon ₁Record at an independent at least wavelength place.Alternatively, intensity can record by five kinds of above-mentioned wavelength, thereby can use the average or the intermediate value of these values.Temperature T ₁, T ₂, T ₃And T ₄The parameter relevant with the blood flow volume is provided.Temperature T ₃Provide and the relevant parameter of heat of passing through radiation delivery.Temperature T ₃And T ₄Provide and the relevant parameter of transmitting by convection current of heat.Absorptance A ₁～A ₆And intensity I ₁The parameter relevant with hemoglobin concentration and hemoglobin saturation with oxygen is provided.

Hereinafter, will the apparatus embodiments of the non-intrusion measurement blood sugar concentration of principle design according to the present invention be described.

Fig. 6 has shown the vertical view according to non-intrusion type blood sugar level measuring equipment of the present invention.Although the skin that uses spherical finger tip in the present embodiment as body surface, also can use other position of health to be used as body surface.

Have an operating means 11, at the upper surface of equipment and be used to place the display device 13 that the measurement mechanism 12 and that will measure finger tip is used for states such as display device state, measured value.Operating means 11 comprises that four buttons from 11a to 11d are used for operating means.Measurement mechanism 12 contains a lid 14, when opening (as shown in the figure), exposes the finger bracket 15 with oval periphery.Finger bracket 15 is furnished with opening terminal 16, contact type temperature sensor 17 and the optical sensor 18 of a radiation temperature transducer.

Fig. 7 has shown the process of operating equipment.When button of push equipment, can open equipment and when circuit carries out preheating, show " preheating " at LCD.Simultaneously, scrutiny program is activated and automatically circuit is checked.When warm-up phase finishes, prompting " putting your finger " on LCD.When the user with his or his finger when being placed on the finger bracket, on LCD, show to count down.After finishing when counting down, prompting " removing finger " on LCD.After the user removed finger according to prompting, LCD showed " deal with data ".Subsequently, display shows blood sugar concentration, and it is stored in the IC-card with date and time.See the blood sugar concentration of demonstration as the user after, he or she presses another button on the equipment.After about 1 minute, equipment is pointed out " finger of putting you " on LCD, so indication equipment has been ready for the test of next round.

Shown measurement mechanism among Fig. 8 in detail.In Fig. 8, (a) be vertical view, (b) be sectional view along the X-X axle among the figure (a), (c) be sectional view along the Y-Y axle among the figure (a), (d) be sectional view along the Z-Z axle among the figure (a).

At first, the equipment by non-intrusion measurement blood sugar concentration according to the present invention being carried out thermometric process is described.The part that contacts with test body (Finger ball) in measurement mechanism is placed a material sheet 21 with high-termal conductivity, for example gold.Be lower than the material of sheet 21 by thermal conductivity, for example the bar-shaped conducting-heat elements 22 made of Polyvinylchloride is thermally connected on the sheet 21 and stretches in the equipment.Temperature sensor comprises a thermistor 23 that is used to measure sheet 21 temperature and serves as the contiguous hygrosensor of Measuring Object.Also have one and be used to measure the conducting-heat elements temperature of separating a segment distance with sheet 21, and serve as the thermistor 24 of the indirect hygrosensor of Measuring Object.Infrared Lens 25 is placed on and makes in the equipment and can see the Measuring Object (Finger ball) that places on the finger bracket 15 by scioptics.Below Infrared Lens 25, transmit window 26 by infrared radiation and placed a pyroelectric detector 27.Another thermistor 28 is placed on the position near pyroelectric detector 27.

Therefore, the temperature sensing of measurement mechanism partly has 4 temperature sensors, and they measure four kinds of following temperature:

(1) temperature of finger surface (thermistor 23): T ₁

(2) temperature of conducting-heat elements (thermistor 24): T ₂

(3) by the radiation temperature of pointing (pyroelectric detector 27): T ₃

(4) room temperature (thermistor 28): T ₄

Light sensor arrangement 18 is measured and is determined necessary hemoglobin concentration of oxygen supply volume and hemoglobin saturation with oxygen.In order to measure hemoglobin concentration and hemoglobin saturation with oxygen, must measure at least absorptance, at least in the catoptrical absorptance at a wavelength place and at least in the photon intensity at a wavelength place at the scattered light at five wavelength places.The accuracy of reflected light absorptance can if possible, can be used average by being measured raising at a plurality of wavelength place.Therefore, in the present embodiment, the reflected light absorptance records at five different wavelength places.By the intensity of mobile photon being measured at a plurality of wavelength place, can also improve the accuracy of measurement, if possible, can use average.Therefore, in the present embodiment, under light, record the intensity of mobile photon near two kinds of wavelength in infrared light wavelength zone.Fig. 8 has shown and has used five light source 35a～35e and three configurations that detector 36～38 is measured.

The end of four optical fiber 31～34 is positioned on the optical sensor 18.Optical fiber 31 is used for optical radiation, and optical fiber 32～34 is used to receive light.Shown in Fig. 8 (c), optical fiber 31 is connected on the optical fiber 31a～31e, has the light emitting diode 35a～35e of five kinds of wavelength respectively in the end of an optical fiber.The other end that receives the optical fiber 32 of light is equipped with photodiode 36.The other end that receives the optical fiber 33 of light is equipped with photodiode 37.The other end that receives the optical fiber 34 of light is equipped with photodiode 38.Light emitting diode 35a emission wavelength is the light of 810nm, and light emitting diode 35b emission wavelength is the light of 950nm.Absorbing wavelength such as wavelength 810nm is, the molar absorption coefficient of taking the haemoglobin of oxygen and do not take the haemoglobin of oxygen under this wavelength equates.At wavelength is to take the haemoglobin of oxygen under the 950nm and do not take between the molar absorption coefficient of haemoglobin of oxygen to have than big difference.Light emitting diode 35c emission wavelength is the light of 520nm, and melanic molar absorption coefficient is bigger under this wavelength.Light emitting diode 35d emission wavelength is the light of 450nm, and bilirubinic molar absorption coefficient is bigger under this wavelength.Light emitting diode 35e emission wavelength is the light of 660nm, and the molar absorption coefficient of absurd creature is bigger under this wavelength.

Five light emitting diode 35a～35e carry out the light emission in the mode of timesharing.The light that light emitting diode 35a～35e sends is radiated on the finger by optical fiber 31.Be radiated at light on the finger by skin reflex, enter the optical fiber 32 that receives light, and finally detected by photodiode 36.Scattered light enters the optical fiber 33 that receives light and is detected by photodiode 37 then.Mobile photon enters the optical fiber 34 that receives light and is detected by photodiode 38 then.These optical fiber that receive light have the photolocking structure, and for example they can prevent directly entering of reflected light and/or scattered light.

When the light of irradiation finger skin during by skin reflex, because skin surface is coarse, the reflected light one way or another carries out scattering.Reflected light is recorded by photodiode 36 and the part scattered light is recorded by photodiode 37.When the light of irradiation finger during by finger skin reflection and scattering, part light transdermal also enters in the tissue, is absorbed by the haemoglobin in the blood mobile in the melanin in the epidermis, the capillary and interfering material cholerythrin and absurd creature then.The measurement data that is provided by photodiode 36 and 37 has reflection R, and can obtain absorptance by log (1/R) approximate treatment.Therefore be the rayed finger of 450nm, 520nm, 660nm, 810nm and 950nm with wavelength, and record the R of every kind of light and calculate log (1/R).Therefore, can record the absorptance A that wavelength is 450nm respectively _D11And A _D21, wavelength is the absorptance A of 520nm _D12And A _D22, wavelength is the absorptance A of 660nm _D13And A _D23, wavelength is the absorptance A of 810nm _D14And A _D24And wavelength is the absorptance A of 950nm _D15And A _D25(wavelength of being surveyed by photodiode 36 is that the catoptrical absorptivity of λ i is A _D1i, the absorptivity of the scattered light of being surveyed by photodiode 37 is A _D2i, and the intensity of the mobile photon of being surveyed by photodiode 38 is I _D3i).

Part light penetrates epidermis and enters in the finger in one's hands, and portion carries out scattering repeatedly within it, and the certain distance d that advances.Thereby can use photodiode 38 to survey mobile photon.

When the hemoglobin concentration of not taking oxygen is [Hb], the hemoglobin concentration of taking oxygen is [HbO ₂], bilirubinic concentration is [Bi], absurd creature concentration be [Tur], when melanic concentration was [Me], wavelength was λ _iThe absorptivity A of scattered light _D2iCan represent with following equation:

$A_{D2i}=a\left\{\right[\mathrm{Hb}]\×A_{\mathrm{Hb}}\left(\mathrm{\λi}\right)+[\mathrm{Hb}{O}_2]\×A_{\mathrm{Hb}{O}_2}\left(\mathrm{\λi}\right)+[\mathrm{Bi}]\×A_{\mathrm{Bi}}\left(\mathrm{\λi}\right)$

$+\left[\mathrm{Tur}\right]\×A_{\mathrm{Tur}}\left(\mathrm{\λi}\right)+\left[\mathrm{Me}\right]\×A_{\mathrm{Me}}\left(\mathrm{\λi}\right)\}\×D\×a_{\mathrm{Rough}}$

$a_{\mathrm{Rough}}=\frac{b\×\mathrm{\Σ}{A}_{D2i}}{\mathrm{\Σ}{A}_{D1i}},$ $D=\frac{1}{\frac{c\×\mathrm{\Σ}{I}_{D3i}}{i}}$

A wherein _Hb(λ _i), A _Hb02(λ _i), A _Bi(λ _i), A _Tur(λ _i) and A _Me(λ _i) be respectively the haemoglobin of not taking oxygen, the haemoglobin of taking oxygen, cholerythrin, absurd creature and melanic molar absorption coefficient.A, b and c are scale-up factors.A _D1iFor wavelength is λ _iThe absorptivity of scattered light, I _D3iFor wavelength is λ _iThe intensity of mobile photon.From top equation, can determine skin surface roughness a _RoughParameter and the parameter D of skin thickness be constant, and can be updated to A _D2iEquation in.The parameter relevant with skin thickness can be determined from the measured value that mobile photon detector obtains, thereby can proofread and correct the influence that skin thickness brings.Because i=1～5, thereby can obtain A _D2iFive equatioies.Connect cube journey by finding the solution these, thereby can obtain five variablees, i.e. [Hb], [HbO ₂], the value of [Bi], [Tur] and [Me].[Hb] and [HbO that obtain from above ₂] can determine hemoglobin concentration [Hb]+[HbO ₂], and hemoglobin saturation with oxygen [HbO ₂]/([Hb]+[HbO ₂]).

In the present embodiment, thus can obtain hemoglobin concentration and hemoglobin saturation with oxygen by under five kinds of wavelength, measuring absorptance.Yet, preferably can record absorptance by adding one or more wavelength, wherein this wavelength is bigger in the molar absorption coefficient difference of taking the oxygen haemoglobin and do not take between the haemoglobin of oxygen, thereby can improve the accuracy of measurement.For example, can add the light that wavelength is 880nm, and will be that hemoglobin concentration and the hemoglobin saturation with oxygen that calculates under 950nm and the 810nm is updated in the above-mentioned equation at wavelength, and be that hemoglobin concentration and the hemoglobin saturation with oxygen that calculates under 880nm and the 810nm calculates its mean value respectively at wavelength.Adopt this method, can improve the accuracy of measurement.

Being used in combination of wavelength is as shown in table 1.

Table 1

	???950nm	???880nm	???810nm	???660nm	??520nm	???450nm
							Example 1	???○		???○			???○
Example 2	???○	???○	???○			???○
							Example 3	???○		???○	???○
Example 4	???○	???○	???○	???○
							Example 5	???○		???○		??○
Example 6	???○	???○	???○		??○
							Example 7	???○		???○	???○		???○
Example 8	???○	???○	???○	???○		???○
							Example 9	???○		???○		??○	???○
Example 10	???○	???○	???○		??○	???○
							Example 11	???○		???○	???○	??○
Example 12	???○	???○	???○	???○	??○	???○
							Example 13	???○		???○	???○	??○	???○
Example 14	???○	???○	???○	???○	??○	???○

As shown in table 1, the configuration of equipment can be adjusted according to the accuracy of expectation, wherein 3～6 kinds of wavelength can be used in combination.If think that measurement result can not be subjected to bilirubinic appreciable impact, just can ignore the wavelength that absorbs relevant 450nm with cholerythrin.The wavelength relevant with melanin absorption is 520nm.The wavelength relevant with absurd creature in the blood is 660nm, and wherein absurd creature mainly is made up of the material of cholesterol, neutral fat and other high fat of blood that forms.If can ignore relative wavelength under the situation that some material can not exert an influence to the result who measures thinking.

Preferably, except the 950nm and 810nm wavelength that are used for hemoglobinometry, can also add and be used for bilirubinic 450nm wavelength, the 660nm wavelength that is used for melanic 520nm wavelength and is used for the blood absurd creature, the light of totally three kinds of wavelength.In general, the 660nm wavelength that is used for the blood absurd creature is only as the third wavelength; Yet, depending on the feature of destination object, the light of other wavelength is perhaps more suitable.

Preferably, can select the light of two kinds of wavelength, form one group of light that contains four kinds of wavelength and measure from the light that is used for bilirubinic 450nm wavelength, is used for melanic 520nm wavelength and is used for the 660nm wavelength of blood absurd creature.As the wavelength of two kinds of interpolations, be used for the only only of bilirubinic 450nm wavelength and the 660nm wavelength that is used for the blood absurd creature.Yet, depending on the feature of measurement target object, the light of other wavelength is perhaps more suitable.

The light that also can use the 950nm and the 810nm that are used for haemoglobin, be used for bilirubinic 450nm wavelength, be used for melanic 520nm wavelength and be used for the 660nm wavelength of blood absurd creature is measured.

Preferably, under the situation of using three kinds, four kinds and five kinds wavelength, the light that can add the 880nm wavelength is used for the measurement of haemoglobin.By so doing, the concentration of determining under every kind of wavelength combinations of taking the oxygen haemoglobin and not taking the haemoglobin of oxygen of taking the oxygen haemoglobin and not taking that the concentration of the haemoglobin of oxygen records when using 880nm wavelength replacement 950nm wavelength can be averaged.

In the following embodiments, the example in the his-and-hers watches 1 13 is described.

Fig. 9 has shown that how processed data are in equipment.Three photo-detectors being furnished with thermistor 23, thermistor 24, pyroelectric detector 27, thermistor 28 and forming according to the equipment of the embodiment of the invention by photodiode 36～38.It is the absorptivity of the light of 810nm, 950nm, 660nm, 520nm and 450nm that photodiode 36 and 37 is measured wavelength.It is the light intensity of 810nm and 950nm that photodiode 38 is measured wavelength.Therefore, this equipment provides 16 types measured value altogether, comprises temperature, heat and optical measurement data.The light that wherein adds wavelength and be 880nm improves measurement precision, and measured value is provided for device 19.

Seven types simulating signal is passed through amplifier A separately ₁～A ₇Supply with analog/digital converter AD ₁～AD ₇Change digital signal into.According to the numerical value of these digital conversion, but calculating parameter x _iBelow (i=1,2,3,4,5) is x _i(e wherein ₁～e ₅Be scale-up factor) specific descriptions:

The parameter that is directly proportional with heat radiation

x ₁＝e ₁×(T ₃) ⁴

The parameter that is directly proportional with thermal convection

x ₂＝e ₂×(T ₄-T ₃)

The parameter that is directly proportional with hemoglobin concentration

x ₃＝e ₃×([Hb]+[HbO ₂])

The parameter that is directly proportional with hemoglobin saturation with oxygen

x ₄＝e ₄×[HbO ₂]/([Hb]+[HbO ₂])

The parameter that is directly proportional with the blood flow volume

x ₅＝e ₅/(t _CONT×(S ₁-S ₂))

Then, by mean value and x _iThe standard deviation calculation normalizing parameter, standard deviation x wherein _iIt is the real data that from a large amount of crowds that labour capacity is arranged and diabetic, obtains.Can be according to following equation from each parameter x _iCalculate normalizing parameter X _i(i=1,2,3,4,5):

$X_i=\frac{x_i-{\stackrel{\‾}{x}}_i}{\mathrm{SD}\left(x_i\right)}$

Here

x _i: parameter

x _i: the mean value of parameter

SD (x _i): the standard deviation of parameter

Five normalizing parameters above using, deriving to calculate to change into is used for the final concentration of glucose that shows.Be used for handling the ROM that calculates the microprocessor that necessary procedure stores carries at equipment.The region of memory that is used for handling calculating is built the RAM in the equipment too in.The result who calculates is displayed on the LCD.

As handling the necessary element of Program for Calculation, the ROM storage is used for determining specially the function of concentration of glucose C.This function definition is as follows.C represents by following equation (1), wherein a _i(i=0,1,2,3,4,5) are determined from many groups measurement data according to following step in advance:

(1) sets up and to be used to represent the multiple regression equation formula that concerns between normalizing parameter and the concentration of glucose C.

(2) by obtaining the normal equation relevant (simultaneous equations) in the equation that obtains by least square method with normalizing parameter.

(3) from the standardization equation, determine coefficient a _iThe value of (i=0,1,2,3,4,5), substitution multiple regression equation formula then.

At first, will represent concentration of glucose C and normalizing parameter X ₁, X ₂, X ₃, X ₄And X ₅Regression equation (1) formulism.

C＝f(X ₁，X ₂，X ₃，X ₄，X ₅)

＝a ₀+a ₁X ₁+a ₂X ₂+a ₃X ₃+a ₄X ₄+a ₅X ₅??......(1)

Then, use least square method to obtain the multiple regression equation formula, this equation can be with the error minimize of the measured value Ci of the concentration of glucose that obtains according to the enzyme electrode method.The quadratic sum of residual error is D, and D can represent by following equation (2):

$D=\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{d_i}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{(C_i-f(X_{i1},X_{i2},X_{i3},X_{i4},X_{i5}))}^2$

$=\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\{C_i-(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5}){\}}^2.......\left(2\right)$

Work as a ₀, a ₂..., a ₅Be 0, the quadratic sum D of the residual error that obtains when equation (2) is used partial differentiation is just for minimum.Therefore, we just obtain following equation:

$\frac{\∂D}{\∂a_0}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0$

$\frac{\∂D}{\∂a_1}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{X}_{i1}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0$

$\frac{\∂D}{\∂a_2}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{X}_{i2}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0$

$\frac{\∂D}{\∂a_3}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{X}_{i3}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0$

$\frac{\∂D}{\∂a_4}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{X}_{i4}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0$

$\frac{\∂D}{\∂a_5}=-2\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{X}_{i5}\left\{C_i(a_0+a_1{X}_{i1}+a_2{X}_{i2}+a_3{X}_{i3}+a_4{X}_{i4}+a_5{X}_{i5})\right\}=0.....\left(3\right)$

As C and X ₁To X ₅Average be respectively C _MeanAnd X _1meanTo X _5meanThe time, because X _Imean=0 (i=1～5) therefore just can obtain equation (4) from equation (1):

a ₀＝C _mean-a ₁X _1mean-a ₂X _2mean-a ₃X _3mean-a ₄X _4mean-a ₅X _5mean

＝C _mean??????????????????????????????????????????????????......(4)

Deviation between normalizing parameter and co-variation are represented by equation (5).At normalizing parameter X _iCo-variation between (i=1～5) and the C is represented by equation (6).

$S_{\mathrm{ij}}=\underset{k=1}{\overset{n}{\mathrm{\Σ}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(X_{\mathrm{kj}}-X_{\mathrm{jmean}})=\underset{k=1}{\overset{n}{\mathrm{\Σ}}}{X}_{\mathrm{ki}}{X}_{\mathrm{kj}}(i,j=\mathrm{1,2},..5).......\left(5\right)$

$S_{\mathrm{iC}}=\underset{k=1}{\overset{n}{\mathrm{\Σ}}}(X_{\mathrm{ki}}-X_{\mathrm{imean}})(C_k-C_{\mathrm{mean}})=\underset{k=1}{\overset{n}{\mathrm{\Σ}}}{X}_{\mathrm{ki}}(C_k-C_{\mathrm{mean}})(i=\mathrm{1,2},..5).......\left(6\right)$

With in equation (4), (5) and (6) the substitution equations (3) and rearrange simultaneous equations (standardization equation) (7).Equation (7) found the solution obtain a ₁To a ₅

a ₁S ₁₁+a ₂S ₁₂+a ₃S ₁₃+a ₄S ₁₄+a ₅S ₁₅＝S _1C

a ₁S ₂₁+a ₂S ₂₂+a ₃S ₂₃+a ₄S ₂₄+a ₅S ₂₅＝S _2C

a ₁S ₃₁+a ₂S ₃₂+a ₃S ₃₃+a ₄S ₃₄+a ₅S ₃₅＝S _3C

a ₁S ₄₁+a ₂S ₄₂+a ₃S ₄₃+a ₄S ₄₄+a ₅S ₄₅＝S _4C

a ₁S ₅₁+a ₂S ₅₂+a ₃S ₅₃+a ₄S ₅₄+a ₅S ₅₅＝S _5C????......(7)

Can obtain constant a by equation (4) ₀The a that obtains thus _i(i=0,1,2,3,4,5) just is stored among the ROM when production equipment.When these equipment of use carry out actual measurement, from the normalizing parameter X of measured value acquisition ₁～X ₅Be used to calculate concentration of glucose in the substitution regression equation (1).

Hereinafter, will the embodiment of the process of calculating parameter Xi be described.The data of using among the embodiment all are to come from healthy crowd.The coefficient that is used for the calculation of parameter equation is to obtain by temperature data that records in advance and optical measurement data.The following equation that is used for calculation of parameter of ROM storage in the microprocessor:

x ₁＝0.98×10 ^-3×(T ₃) ⁴

x ₂＝1.24×(T ₄-T ₃)

X ₃＝1.36×([Hb]+[HbO ₂])

$x_4=2.67\×\left(\frac{\left[\mathrm{Hb}{O}_2\right]}{\left[\mathrm{Hb}\right]+\left[\mathrm{Hb}{O}_2\right]}\right)$

$x_5=1.52\×{10}^6\×\left(\frac{1}{t_{\mathrm{CONT}}\×(S_1-S_2)}\right)$

For example work as T ₃=36.5 ℃ are used as measured value when being updated in the above-mentioned equation, obtain x ₁=1.74 * 10 ³Work as T ₄=19.7 ℃ when being updated in the above-mentioned equation, obtain x ₂=2.08 * 10.Then, calculating x ₃Before, need obtain [Hb] and [HbO earlier ₂].The coefficient that is used for the concentration computing formula is determined by the light scattering absorption coefficient of every kind of material recording in advance.Use this equation, under the condition of using five kinds of wavelength measurements, can determine [Hb] and [HbO by finding the solution following simultaneous equations ₂]

A _{D2_450}＝9.74×10 ¹＝0.87{60,000×[Hb]+60,000×[HbO ₂]+55,000×[Bi]

+160×[Tur]+1,900×[me]}×0.93×0.85

A _{D2_520}＝4.90×10＝0.87{33,000×[Hb]+30,000×[HbO ₂]+54×[Bi]

+130×[Tur]+1,300×[me]}×0.93×0.85

AD _{2_660}＝1.40＝0.87{3,000×[Hb]+300×[HbO ₂]+30×[Bi]

+100×[Tur]+470×[me]}×0.93×0.85

A _{D2_810}＝1.67＝0.87{800×[Hb]+800×[HbO ₂]+3×[Bi]

+60×[Tur]+190×[me]}×0.93×0.85

A _{D2_950}＝1.98＝0.87{750×[Hb]+1,150×[HbO ₂]+2×[Bi]

+30×[Tur]+60×[me]}×0.93×0.85

$a_{\mathrm{Rough}}=0.85=\frac{1.35\×(9.74\×{10}^1+4.90\×10+1.40+1.67+1.98)}{(1.55\×{10}^1+7.78\×10+2.22+2.65+3.14)}$

$D=0.93=\frac{1}{\frac{1.06\×(1.02+1.01)}{2}}$

Find the solution this Simultaneous Equations and can obtain [Hb]=0.09mmol/L and [HbO ₂]=2.21mmol/L.Thereby can calculate x ₃=3.13 and x ₄=2.57.Then, substitution S ₁=1.76 * 10 ², S ₂=1.89 * 10 and tCONT=22 second, calculate x ₅=4.40 * 10 ²

Similarly, use at the same time under the condition of light of four kinds of wavelength 950nm, 810nm, 660nm and 450nm, we obtain following Simultaneous Equations:

A _{D2_450}＝9.74×10 ¹＝0.87{60,000×[Hb]+60,000×[HbO ₂]+53,000×[Bi]

+190×[Tur]}×0.93×0.85

A _{D2_660}＝1.40＝0.87{3,000×[Hb]+300×[HbO ₂]+30×[Bi]

+146×[Tur]}×0.93×0.85

A _{D2_810}＝1.67＝0.87{800×[Hb]+800×[HbO ₂]+3×[Bi]

+78×[Tur]}×0.93×0.85

A _{D2_950}＝1.98＝0.87{750×[Hb]+1,150×[HbO ₂]+2×[Bi]

+34×[Tur]}×0.93×0.85

$a_{\mathrm{Rough}}=0.85=\frac{1.35\×(9.74\×{10}^1+1.40+1.67+1.98)}{(1.55\×{10}^1+2.22+2.65+3.14)}$

$D=0.93=\frac{1}{\frac{1.06\×(1.02+1.01)}{2}}$

Wherein the absorptivity in each equation all is different from the absorptivity of the Simultaneous Equations when using five kinds of wavelength.This is owing to the existence that lacks melanin institute absorbing wavelength light, thereby the influence that melanin brings in arithmetic expression is replaced by the influence of another kind of material.

Find the solution this Simultaneous Equations and can obtain [Hb]=0.10mmol/L and [HbO ₂]=2.21mmol/L.

Similarly, use at the same time under the condition of light of three kinds of wavelength 950nm, 810nm and 660nm, we obtain following Simultaneous Equations:

A _{D2_660}＝1.40＝0.87{3,000×[Hb]+300×[HbO ₂]+140×[Tur]}×0.93×0.85

A _{D2_810}＝1.67＝0.87{800×[Hb]+800×[HbO ₂]+80×[Tur]}×0.93×0.85

A _{D2_950}＝1.98＝0.87{750×[Hb]+1,150×[HbO ₂]+34×[Tur]}×0.93×0.85

$a_{\mathrm{Rough}}=0.85=\frac{1.35\×(1.40+1.67+1.98)}{3.14+2.65+2.22}$

$D=0.93=\frac{1}{\frac{1.06\×(1.02+1.01)}{2}}$

Find the solution this Simultaneous Equations and can obtain [Hb]=0.12mmol/L and [HbO ₂]=2.22mmol/L.

The measured result of light according to five kinds, four kinds and three kinds wavelength that use simultaneously calculates hemoglobin concentration [[Hb]+[HbO ₂]] be respectively 2.30mmol/L, 2.31mmol/L and 2.34mmol/L.Use the intrusive mood method simultaneously, promptly the hemoglobin concentration that records of the method by blood sample is 2.28mmol/L.These results show and use four kinds of wavelength to approach the hemoglobin concentration that the method by blood sample records more than the hemoglobin concentration of using three kinds of wavelength to calculate, and use five kinds of wavelength to approach the hemoglobin concentration that the method by blood sample records more than the result who uses four kinds of wavelength to calculate.Therefore these results show that the accuracy of measurement can be improved by the number that increases employed wavelength.

Next step is with top resulting parameter x ₁～x ₅Can obtain X after the standardization ₁～X ₅Suppose that parameter distributions is a normal state, the value of 95% normalizing parameter is distributed between-2～+ 2 so.For example, in the example 13 of table 1, normalizing parameter can be determined by following equation:

$X_1=-0.06=\frac{1.74\×{10}^3-1.75\×{10}^3}{167}$

$X_2=0.04=\frac{2.08\×10-2.06\×10}{5}$

$X_3=0.05=\frac{3.13-3.10}{0.60}$

$X_4=-0.12=\frac{2.54-2.60}{0.50}$

$X_5=0.10=\frac{4.40\×{10}^2-4.52\×{10}^2}{120}$

From top equation, can obtain normalizing parameter X ₁=-0.06, X ₂=+0.04, X ₃=+0.05, X ₄=-0.12 and X ₅=+0.10.

Hereinafter, will the embodiment that calculate the concentration of glucose process be described.Coefficient in regression equation (1) is to determine in the mass data that obtains from a large amount of crowds that labour capacity is arranged and diabetic in advance, and the storage of the ROM in the microprocessor is used to calculate the following equation of concentration of glucose:

C＝99.4+18.3×X ₁-20.2×X ₂-23.7×X ₃-22.0×X ₄-25.9×X ₅

With X ₁～X ₅Substitution obtains C=96mg/dl.In test to the diabetic, substitution typical case's measured value such as X in aforesaid equation ₁=+1.15, X ₂=-1.02, X ₃=-0.83, X ₄=-0.91 and X ₅=-1.24 calculate C=213mg/dl.

Hereinafter, glucose concentration value that will record the enzyme electrode method by routine and the glucose concentration value that records with method of the present invention compare.In the enzyme electrode method, thereby blood sample and reagent are reacted and measure the electron amount that produces and determine concentration of glucose.When using the enzyme electrode method when the crowd that labour capacity is arranged being tested the glucose concentration value that obtains as 89mg/dl, the normalizing parameter of using the present invention to record simultaneously is X ₁=-0.06, X ₂=+0.04, X ₃=+0.07, X ₄=-0.10 and X ₅=+0.10.To obtain C=95mg/dl in these value substitution aforesaid equations.On the other hand, when using the enzyme electrode method when the diabetic being tested the glucose concentration value that obtains as 238mg/dl, the normalizing parameter of using the present invention to record simultaneously is X ₁=+1.15, X ₂=-1.02, X ₃=-0.95, X ₄=-1.05 and X ₅=-1.24, will obtain C=218mg/dl in these value substitution aforesaid equations.These results show that the method for using among the present invention can obtain the concentration of glucose of pinpoint accuracy.

Fig. 9 has marked and drawed a plurality of patients' glucose concentration value.The glucose concentration value that calculates according to the present invention is presented on the longitudinal axis, and the glucose concentration value that records by the enzyme electrode method is presented on the transverse axis.Use the method among the present invention, can obtain correlativity (related coefficient=0.9434) preferably by measuring oxygen supply volume and blood flow volume as can be seen.

Therefore, the present invention can provide blood sugar concentration is carried out equipment and the method that the non-intrusion type high precision is measured.

Claims (20)

1. blood sugar level measuring equipment comprises:

One apparatus for measuring amount of heat is used to measure a plurality of shell temperatures, to obtain to be used for and to calculate from the information of the heat of the heat of the relevant convective heat transfer of the heat of body surface dissipation and radiation heat transfer;

One blood flow volume measurement device is used to obtain the information of blood flow volume;

One optical measuring device, be used for obtaining the hemoglobin concentration and the hemoglobin saturation with oxygen of blood, the light that this unit comprises the light source that can generate at least three kinds of different wavelengths of light, send by light source shines an optical system and at least three kinds of different photo-detectors of body surface, is used to survey the light that is radiated on the body surface;

One memory storage, be used to store blood sugar level and and the corresponding individual parameter of a plurality of temperature, blood flow volume, blood hemoglobin concentration and hemoglobin saturation with oxygen between concern;

One calculation element is used for the measured value that apparatus for measuring amount of heat, blood flow volume measurement device and optical measuring device provide is converted to parameter, and this calculation element is also used these parameters in the relation that memory storage stores and calculated blood sugar level; And

One display device is used to show the blood sugar level that is calculated by computing equipment.

2. blood sugar level measuring equipment according to claim 1 is characterized in that, described photo-detector comprises and is used to survey catoptrical first photo-detector of body surface; Be used to survey second photo-detector of body surface scattered light; And survey by body surface and enter skin and the 3rd photo-detector of the light that from body surface, passes.

3. blood sugar level measuring equipment according to claim 2 is characterized in that, described light source comprises a plurality of light emitting diodes that are used to launch different wavelengths of light; Wherein, optical system comprises that the illumination that light emitting diode is sent is mapped to first optical fiber at the illuminated position of body surface; And second optical fiber, it will be radiated at emission light on the body surface and be delivered to first, second and the 3rd photo-detector.

4. blood sugar level measuring equipment according to claim 3 is characterized in that, the optical fiber top of transmitting light to the three detectors contacts with body surface.

5. blood sugar level measuring equipment according to claim 2 is characterized in that light source produces the light of certain wavelength, at this wavelength place, takes the oxygen haemoglobin and equates with the molar absorption coefficient of not taking the oxygen haemoglobin; Produce the light of first kind of wavelength, be used to survey the difference of taking the oxygen haemoglobin and not taking absorptivity between the oxygen haemoglobin; And produce the light that is absorbed by cholerythrin.

6. blood sugar level measuring equipment according to claim 5 is characterized in that the light of certain wavelength of generation is absorbed by absurd creature in the blood or melanin.

7. blood sugar level measuring equipment according to claim 5 is characterized in that, the light of certain wavelength of generation absorbs by the absurd creature in the blood or by melanin.

8. according to claim 5,6 or 7 described blood sugar level measuring equipments, it is characterized in that, produce the light of second kind of wavelength, be used to survey the difference of taking the oxygen haemoglobin and not taking absorptivity between the oxygen haemoglobin.

9. blood sugar level measuring equipment according to claim 5 is characterized in that the light of each wavelength of the suffered irradiation of body surface is surveyed by second detector.

10. blood sugar level measuring equipment according to claim 9 is characterized in that, because the error that the body surface roughness is brought can use the measured absorptivity of first and second photo-detectors to proofread and correct.

11. blood sugar level measuring equipment according to claim 9 is characterized in that, because the error that skin thickness brought can use the measured light intensity of the 3rd detector to proofread and correct.

12. blood sugar level measuring equipment according to claim 11, it is characterized in that correction is to be undertaken by asking for standard substance, absorptivity that leaves then and the absorptance that is recorded by the 3rd detector that prior use the 3rd detector measurement enters known thickness.

13. blood sugar level measuring equipment according to claim 1 is characterized in that, the blood flow volume measurement device comprises a body surface contact device; One contiguous hygrosensor, itself and body surface contact device are adjoining; One indirect temperature detector is used to measure the temperature that has a distance with the body surface contact device; An and heat conducting element that connects body surface contact device and indirect temperature detector;

14. blood sugar level measuring equipment according to claim 1 is characterized in that, apparatus for measuring amount of heat comprises and is used to measure the environment temperature detector of ambient temperature and measure from the photothermal bolometer detector of body surface.

15. blood sugar level measuring equipment according to claim 2 is characterized in that, enters into the light of skin and is sent to the 3rd photo-detector by the light that body surface comes out from the exit by a light path with light blocking environment by body surface.

16. a blood sugar level measuring equipment comprises:

One ambient temperature detector is used to measure the temperature of surrounding environment;

One contact device that contacts with body surface;

One radiation temperature detector is used to measure the radiation heat that comes from body surface;

One with the adjoining contiguous hygrosensor of body surface contact device;

One indirect temperature detector is used to measure the temperature that has a distance with the body surface contact arrangement;

One heat conducting element is used to connect body surface contact device and indirect temperature detector;

One can produce the light source of the light of at least three kinds of different wave lengths, and wherein the light of three kinds of different wave lengths is 810nm, 950nm and the third wavelength;

One optical system, the rayed body surface that it uses light source to send;

At least three kinds of different photo-detectors are used to survey the light that shines body surface;

One memory storage, be used to store ambient temperature detector, radiation temperature detector, contiguous hygrosensor, indirect temperature detector and at least three kinds of different photo-detectors separately output and the relation between the blood sugar level;

One calculation element, it uses various outputs and calculates blood sugar level with reference to the relation that is stored in the storage unit; One display device is used to show the blood sugar level that is calculated by computing equipment.

17. blood sugar level measuring equipment according to claim 16 is characterized in that, only the selecting from the group that 450nm, 660nm, 520nm and 880nm form of the third wavelength.

18. blood sugar level measuring equipment according to claim 16, it is characterized in that, light source produces the light of the 4th kind of wavelength, and it is used in combination with the light of the third wavelength, only the selecting from the group that 450nm, 660nm, 520nm and 880nm form of two kinds of wavelength that wherein are used in combination.

19. blood sugar level measuring equipment according to claim 16, it is characterized in that, light source produces the light of the 4th kind and the 5th kind wavelength, it is used in combination with the light of the third wavelength, only the selecting from the group that 450nm, 660nm, 520nm and 880nm form of three kinds of wavelength that wherein are used in combination.

20. blood sugar level measuring equipment according to claim 16 is characterized in that, at least a photo-detector is surveyed the light that enters into skin and come out from exit portion by a light path with light blocking environment by body surface.

Images